Soluble tablets

ABSTRACT

A LUBRICATING AGENT SUITABLE FOR USE IN THE PREPARATION OF WATER SOLUBLE TABLETS AND A METHOD OF ITS PREPARATION ARE DISCLOSED. THE AGENT COMPRISES IN COMBINATION A COMPOSITIONS OF SUBSTANTIALLY ANHYDROUS SODIUM SULFATE AND A DIMETHYLPOLYSILOXANE.

ABSTRACT oF-mn DISCLOSURE A lubijicating jag'entsuitable for-use in thepreparation ofwater soluble tablets and-amethod of its preparation aredisclosed. The agent comprises in combination a composition ofsubstantially anhydrous sodium sulfate and a f y p lysiloxane.

, is a division of appfication Ser. N0. 86,946, filed N it I1Q Q .QiQiY.UQS-..PaP-.NO, 35712 dated 6,

SUMMARY OF THE INVENTION l: This'inve'rrtion relates to the productionof tablets. More particularly, "this invention" 'is' concerned with anew and useful lubricating agent 'siiit'able'for use in preparing watersoluble tablets and to a *processfor manufacturing this :ag'ent.:-

5. ."sirlti is a common prac es in tablet manufacture to incorporate anactive substance;; into an, appropriate excipient. The "excipient, inturn, is usually made up of inert powders, one or more lubricantgwand,if necessary, one or more agentsfavoring thedisintegration of thetablets. When ,water solublg tablets are to be manufactured, the choiceof the; appropriate lubricant .presents a difficulty in view of thenecessity of employing water soluble, tasteless substances which are nottoxic and do not foam. These requirements reduce the number of usefullubricants con- 'irly'whena direct'compression is to be nthe'mrifacturingof soluble tablets the choice of a u aiifiis essential als'oin order to carry out 'th coi'n'pr ssion without seizure of the usedpunches and 't'o nialr'e the 'tablets-comewubof the machine with a"smooth surface withou'filosin'g fragments which could adhere td thenioving'part (if the machine. Thesubjectof-the present invention is anew lubricating "agent for use in the manufacturing of soluble tablets,which=-lubricant is=acomposition of substantially anhydrou's'sodium-sulfate-havingin combination therewith from about -2 to about 7'percent by weight of a dimethylpoly'siloxanehaving maximum viscosity ofabout 1,000 mi ok i i further purpose of thein'vention consists in aprocr preparin'g -the above-quality ofanhydrous sodiumsulfatebydissolving the dimethylpolysiloxane in' an appropriate volatile"-organic'-'-solvent,1 wetting the desired quantity -of-anhydroussodiumsulfate with the obtained solution and evaporating "olfthe solvent. Any common solvent-can be :used asthe volatile organicsolvent provided the solubility in" i it of the dimethylpolysiloxaneis-osufiicient"to carryf'out the operation in a reasonable volume ofliquid. In practice, it is'preferred to employ .ahalogenatedhydrocarbon,such -asmethylene dichloride, chloroform,':carbon-tetrachloride,"and thelike which are lrelativelyrinexpensiveand not easily flammable. Afterevaporationoflthe solventathe residue ordinarily is ground 3,819,824Patented June 25, 1974 in a mill. This operation can be performedwithout any difiiculty due to the change in the physical properties ofthe anhydrous sodium sulfate. The obtained powder can be passed througha stainless steel sieve with meshes of convenient size, such as -125mesh per inch. Grinding and sieving can be preferably performedsimultaneously in a suitable apparatus, such as the well-known Fitzmill; or sieving can be simply carried out by hand. The modifiedanhydrous sodium sulfate is then used in manufacture of soluble tabletsaccording to well-known techniques.

To the mass ready for compression, which can be used in the granulatedform or as such, the modified anhydrous sodium sulfate is added in theproportion commonly used for the lubricant. The resulting mixture ofpowders is tabletted by means of normal steel punches employing commontabletting and rotative machines without any supplementary device forthe continuous lubrication of the punches during the compression,obtaining in this way a considerable increase of the output for timeunit.

A particular utility of the modified anhydrous sodium sulfate can benoticed during the manufacture of soluble effervescent tablets in whichare incorporated the usual ingredients destined to the production ofcarbon dioxide evolution, e.g., alkalies, carbonate or hydrogencarbonate, tartaric acid, citric acid or their partial salts with alkalimetals. Moreover, the modified anhydrous sodium sulfate shows aparticular utility when, as excipients, are used carbohydrates and theirderivatives as a hexitol or a pentitol, such as xylitol, mannitol,sorbitol, etc. or a hexose or a pentose, as for example, glucose,mannose, sorbose, xylose and others; or a reducing disaccharide,chemically defined as hexosylhexose, such as maltose or a nonreducingdisaccharide, chemicaly defined as hexosylhexoside, such as sucrose orlactose.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The following Examples givesome indications for preparing the modified anhydrous sodium sulfate andfor using it in manufacture of soluble tablets.

Example 1 (a) A solution of dimethylpolysiloxane (500 centistokesviscosity) 2.4 g. and methylene dichloride 24.0 g. is blended withfinely powdered anhydrous sodium sulfate 57.6 g. The mass is dried at 35C. in an air stream until the solvent is removed. The residue is passedthrough a mesh stainless steel sieve.

(b) In a mixer there are blended crystalline dry xylitol 500 g. andsodium carboxymethylcellulose 20 g.

The mixtures obtained according to (a) and (b) are mixed and theresulting mass is compressed in a tabletting machine provided withstainless steel punches to manufacture tablets 280 mg. in weight. Thecarboxymethylcellulose employed had a degree of substitution rangingfrom 0.34 to 0.40 and a sodium content between 4.1 and 4.8 percent. Theresulting tablets are shiny and smooth. The dissolution time in water isfrom 30 seconds to one minute.

Example 2 (a) A solution of dimethylpolysiloxane (350 centistokesviscosity) 5.5 g. and methylene dichloride 50 g. is blended with finelypowdered anhydrous sodium sulfate 163 g. The mass is dried at 35 C. inan air stream until the solvent is removed. The residue is pased througha 75 mesh stainless steel sieve.

(b) In a mixer the following ingredients are blended:

ascorbic acid 525 g., anhydrous-citric acid 584 g.,"sodiurri" Example 3(a) A solution of dimethylpolysiloxane (200 centistokes viscosity) 4.8g. and methylene dichloride 4 8.0 g. is blended with finely powderedanhydrous sodium sulfate 155.2 g. The mass is dried at 35 C. in an airstream until the solvent is removed. The residue is passed through a 75mesh stainless steel sieve.

(b) In a mixer mannitol 1,840 g. and sodium carboxymethylcellulose 90 g.are blended with the mixture prepared according to (a). The resultingmass is compresed in a tabletting machine provided with stainless steelpunches to manufacture tablets weighing 0.5 g. The tablet dissolutiontime in water is between 30 seconds and one minute.

Example 4 (a) A solution of dimethylpolysiloxane (1,000 centistokesviscosity) 7.2 g. and methylene dichloride 72.0 g. is blended withfinely powdered anhydrous sodium sulfate 112.8 g. The mass is dried at35 C. in an air stream until the solvent is removed. The residue ispassed through a 75 mesh stainless steel sieve.

(b) In a mixer sucrose 880 g. and sodium carboxymethylcellulose 40 g.are blended with the mixture prepared according to (a), and theresulting mass is compressed in a tabletting machine provided withstainless steel punches to manufacture tablets weighing 1 g. The tabletsare shiny and smooth. The tablet dissolution time in water is betweenone and two minutes.

Example 5 (a) In a blender are mixed the following ingredients: sucrose230 g., ascorbic acid 187 g., saccharin 16 g., citric acid (anhydrous)330 g. and sodium bicarbonate 480 g.

(b) The mass (a) is blended with polyvinylpyrrolidone 60 g. andmethylene dichloride 960 g. and granulated.

(c) A solution of dimethylpolysiloxane (400 centistokes viscosity) 2.1g. and methylene chloride 21 g. is added to 50.4 g. of anhydrous sodiumsulfate and the mass is dried at 35 C. in an air stream until thesolvent is eliminated. The residue is passed through a stainless steelsieve of 75 mesh per inch.

((1) The granulate (b) is blended thoroughly with the power (c) togetherwith 75 g. of orange flavor powder and the resulting mass is compressedin a tabletting machine with stainless steel punches to form tablets ofabout 1.6 g. weight. The tablets are bright and smooth. They dissolve inwater in about 2 minutes.

Example 6 (a) A granulatc is prepared from disodium citrate 365 g.,polyvinylpyrrolidone 18 g., and deionized water 36 g.

(b) Separately the following mixture is granulated: sodium bicarbonate139 g., polyvinylpyrrolidone 3 g. and deionized water g.

(c) A solution of dimethylpolysiloxane (600 centistokes viscosity) 0.9g. and chloroform 9 g. is added to anhydrous sodium sulfate 21.52 g. andthe mass is dried at 35 C. The residue is passed through a sieve 100mesh per inch.

(d) The following ingredients are accurately mixed: granulated mixture(a) 383 g., granulated mixture (b) 142 g., l a-methylprednisone hem ture(c) 22.4 g. The mass is compressed to form effervescent tablets of 600mg. weight.

7 ha P if F 1 Water soluble effervescent. tablets each weighinggl fi g.are prepared through the abovedescrib'ed procedure rom the followingingredients:

Mannitol Tartrazine yellow Citric acid, anhydrous Sodiumbicarbonate-11.;

Saccharin Polyvinylpyrrolidone Anhydrous sodium sulfateDimethylpolysiloxane Ethyl alcohol Metoclopramide HCl i x m l A simplepreparation of effervescent tablets is carried out as describedin"'the'=foregoing Exaimplesg to .obtatn tablets with thefollowing-composition:

Citric acid, anhydrous Sodium bicarbonate Acetylsalicylic acid Anhydroussodium su ate W1 siloxane (350 centistokes visco We claim: 4 v 1. In aprocess for. the preparatrong o fervescent tablets which compris'esproviding a" sol d position comprising an active substanceefienyescencouple and an excipient-for compression into tabl e ts, u saidcomposition with a lub ricating agentinthe-fo in powder, and compressingthe.resulting mixture lets; the improvement which .icqrppris s wet 'pgsubstan tially anhydrous sodiumv sulfate.witll.,.a,solutior5pfa;.;dimethylpolysiloxane in avolatileorga solvet,;.said-dimethylpolysiloxane having a maxirnlu n -v scosity -of abgq1,000 centistokes, the ratio;of-said.dimethflpqly silpxar e to saidsodium sulfate rangingfrorn.abgutljQaboubfl parts ofdimethylpolysiloxane. per,;10 0par.ts of sodium-; sttlfate, and removingsaid volatile', organiq solveng, hereby a solid lubricating agentconsisting essentially of zthqt fia substantially anhydrous sodiumsglfate, and 1116 said dimethylpolysiloxane ;is obtained; -;and-'-adingaid-hilarieating agenttotsaid comp sition asr tesd ss ntiall icant andcompressingtheresulting rriixturejnto tablets 7'.-

2. The process of fllaimlgwherein- 'thegcornpositio to be compressed isin granulatedforrn. r 3. The process of Claim 1-wherem,the

excipient. 1

prises a member of thegrqup consisting of. hexitolsgpenb comprising anactive, substance etfervescent couple andja lubricant, the improvementwherein.--the "sole-. Tessential lubricant is a composition-.-consisting essentiallytzoftgsubr stantially anhydrous sodium sulfate incombination with a 5 dimethylpolysiloxane, the weight proportions ofsaid di- 3,240,712 methylpolysiloxane/sodium sulfate ranging from about2 3,125,519 to about 7/ 100, said dimethylpolysiloxane having a maximum'viscosity of about 1,000 centistokes.

5 617,684 References Cited 657,156 962,252

UNITED STATES PATENTS 6 3/ 1966 Schulerud et a1. 252-138 3/1964 Grave etal. 252-11 FOREIGN PATENTS 8/ 1962 Belgium. 6/ 1965 Belgium. 7/1964Great Britain.

SHEP K. ROSE, Primary Examiner

